The present invention relates to a process for the preparation of 1,3-dihydroxy-2-nitropropane.
1,3-Dihydroxy-2-aminopropane, also called serional in the literature, is a small, physiologically well compatible base which has gained increasing signifiance as an intermediate for the production of physiologically very highly compatible X-ray contrast media. In this regard, see German Pat. No. 2,547,789 and German Patent Application No. P 26 28 517.6, corresponding to U.S. Application Ser. No. 806,384, filed on June 14, 1977, which disclose the advantageous properties of serionl-containing X-ray contrast media and processes for the preparation thereof. The disclosures of these documents are incoporated by reference herein with respect to their discussion of this use of serinol.
Herefore, the literature has described only extremely expensive multistage syntheses for the preparation of serinol. Consequently, these are technically and industrially useless. Moreover, they yield only low quantities of product.
In one process, serionl oxalate or hydrochloride was isolated in a 15% yield by Piloty el al ("Ber. dtsch. Chem. Ges." [Reports of the German Chemical Society] 30: 2061 [1897]). They started with dihydroxyacetone, prepared the dihydroxyacetone oxime and subsequently reduced this with sodium amalgam.
A different synthesis is described by Schmidt et al ("Ber. dtsch. Chem. Ges." 52: 389 [1919]). In this process, paraformaldehyde and nitromethane are condensed in the presence of aqueous potassium hydroxide solution, and the reaction product is converted without isolation of the intermediates into the sodium salt of 1,3-dihydroxy-2-nitropropane. The sodium salt, serving as the starting compound for the subsequent reaction steps, is obtained in a 91% yield with 2 moles of methanol. To convert the nitro group into the amino group, it is necessary in accordance with this reference to produce the free nitro compound prior to hydrogenation.
The conversion of the sodium salt of a nitro compound into the free nitro compound, however, is quite generally accompanied by secondary reactions, which can be so predominant as to even become the primary reaction. According to Houben-Weyl, vol. X/1: 456 (1969), the free nitropropanediol cannot be produced with mineral acids; or, if it is so produced, the reaction yields only very low quantities of desired product. Schmidt el al react the Na salt with salicylic acid in ether, thus isolating the not-yet-completely pure 1,3-dihydroxy-2-nitropropane in a 59% yield. The subsequent catalytic hydrogenation is best accomplished, in accordance with the Schmidt et al reference, with a pelladium/barium sulfate catalyst, in an oxalic acid solution. In a neutral solution, the hydrogenation takes place very reluctantly, and in an alkaline or mineral acid solution, the hydrogenation fails altogether.
From the oxalic acid solution, the neutral oxalate of 1,3-dihydroxy-2-aminopropane is isolated in a 93% yield. Finally, the serinol is liberated therefrom as a viscous liquid by the precipitation of barium oxalate by addition of barium hydroxide solution. No data regarding the yield from this completeprocess are set forth.